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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 October to 04 November 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
purity of test item not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Physical state: liquid

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Company of Calco, Italy.
- Age at receipt: 40 days
- Weight at reeipt: Males: 100-125 g; Females: 75-100 g
- Fasting period before study: Animals were fasted 16 h before the administration of test item.
- Housing: Animals were housed in stainless steel wire grill cages suspended over automatically flushed racks.
- Diet: Pellet-form feed, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature: 22-24 °C
- Humidity: 60 ± 20 %
- Air changes: 15 air changes per hour
- Photoperiod: Subdued natural lighting

IN-LIFE DATES: 18 October to 04 November 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100, 200, 250, 310, 350 and 390 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION
Estimated amounts of the test item were weighed for each dosage and dissolved in a calculated volume of corn oil (Commercial brand: CARAPELLI) so that the concentration of the dosing solution was kept constant for all dosage levels and the amount received by each animal did not exceed 10 mlLkg bw.
Doses:
Preliminary study: 2000, 3000 and 5000 mg/kg bw
Main study: 1000, 2000, 2500, 3100, 3500 and 3900 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 1 animal/sex/dose
Main study: 5 animals/sex/dose
Control animals:
yes
Remarks:
corn oil
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Following administration, the animals were observed for mortality and toxic effects twice during the first day and once daily thereafter for 14 days.
- Frequency of weighing: The body weight of the animals was recorded on the day before the final trial, the day of the final trial and on days 1, 2, 4, and 14 after administration.
- Necropsy of survivors performed: Yes; all animals dying during the observation and those killed on day 14 were subjected to gross pathology to detect possible lesions.
Statistics:
Data was evaluated according to the method of Litchfield and Wilcoxon (1949).

Results and discussion

Preliminary study:
Mortality was observed in 1/2, 2/2 and 2/2 animals at 2000, 3000 and 5000 mg/kg bw, respectively.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 320 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits: 2010 - 2660 mg/kg bw
Mortality:
Death occurred within two days after administration in 0, 3, 5, 8, 10 and 10 animals (the mortality percentage was 0, 30, 50, 80, 100 and 100) at 1000, 2000, 2500, 3100, 3500 and 3900 mg/kg bw, respectively.
Clinical signs:
- All animals displayed listlessness during the initial 24 h after treatment. In those at the higher doses, this lasted up to 48 h.
- Some animals also manifested chromodacryorrhea.
- For the remaining observation period, no untoward signs were noted among the survivors.
Body weight:
Only a slight body weight loss was observed among the animals at higher dosages (2500 and 3100 mg/kg bw).
Gross pathology:
All animals that died during the experiment were found to have gastro-intestinal and pulmonary hemorrhaging and in some cases both were observed.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, the oral LD50 for test item is 2320 mg/kg bw (95% confidence limits: 2010 - 2660 mg/kg bw) in rats therefore the substance should not be classified according to the Regulation (EC) No. 1272/2008 (CLP). Based on the mortality observed, it should be classified in Category 5 according to the GHS criteria.
Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, CD rats (5/sex/dose) were given a single oral (gavage) dose of test item in corn oil at 0, 1000, 2000, 2500, 3100, 3500 and 3900 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. The dose levels selected on the basis of results of preliminary study (2000, 3000 and 5000 mg/kg bw; 1/sex/dose).

 

All animals displayed listlessness during the initial 24 h after treatment. In those at the higher doses, this lasted up to 48 h. Some animals also manifested chromodacryorrhea. For the remaining observation period, no untoward signs were noted among the survivors. Death occurred within two days after administration in 0, 3, 5, 8, 10 and 10 animals (the mortality percentage was 0, 30, 50, 80, 100 and 100) at 1000, 2000, 2500, 3100, 3500 and 3900 mg/kg bw, respectively. Only a slight body weight loss was observed among the animals at higher dosages (2500 and 3100 mg/kg bw). All animals that died during the experiment were found to have gastro-intestinal and pulmonary hemorrhaging and in some cases both were observed.

 

The combined LD50: 2320 mg/kg bw (95% confidence limits: 2010 - 2660 mg/kg bw).

 

Under the test conditions, the oral LD50 for test item is 2320 mg/kg bw (95% confidence limits: 2010 - 2660 mg/kg bw) in rats therefore the substance should not be classified according to the Regulation (EC) No. 1272/2008 (CLP). Based on the mortality observed, it should be classified in Category 5 according to the GHS criteria.